title: Lipopolysaccharide-induced multinuclear cells: increased internalization of polystyrene beads and possible signals for cell fusion.
abstract: A murine macrophage-derived line, RAW264.7, becomes multinuclear on stimulation with lipopolysaccharide (LPS), an outer membrane component of Gram-negative bacteria. These multinuclear cells internalized more polystyrene beads than mononuclear cells or osteoclasts (Nakanishi-Matsui, M., Yano, S., Matsumoto, N., and Futai, M., 2012). In this study, we analyzed the time courses of cell fusion in the presence of large beads. They were internalized into cells actively fusing to become multinuclear. However, the multinuclear cells once formed showed only low phagocytosis activity. These results suggest that formation of the multinuclear cells and bead internalization took place simultaneously. The formation of multinuclear cells was blocked by inhibitors for phosphoinositide 3-kinase, phospholipase C, calcineurin, and c-Jun N-terminal kinase. In addition, interleukin 6 and 10 also exhibited inhibitory effects. These signaling molecules and cytokines may play a crucial role in the LPS-induced multinuclear cell formation.
authors.affiliation: Department of Biochemistry, Faculty of Pharmaceutical Sciences, Iwate Medical University, Yahaba, Iwate 028-3694, Japan. Electronic address: nakanim@iwate-med.ac.jp.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Nakanishi-Matsui
authors.forename: Shio
authors.initials: S
authors.lastname: Yano
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Futai
mesh_terms: D000818:Animals; D065095:Calcineurin Inhibitors; D002459:Cell Fusion; D002460:Cell Line; D002467:Cell Nucleus / Q000648:ultrastructure*; D016753:Interleukin-10 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000008:administration & dosage; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D008863:Microspheres; D010587:Phagocytosis; D019869:Phosphatidylinositol 3-Kinases / Q000008:administration & dosage; D011137:Polystyrenes / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
chemical_list: D065095:Calcineurin Inhibitors; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011137:Polystyrenes; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D019869:Phosphatidylinositol 3-Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D010738:Type C Phospholipases
keywords: Cell–cell fusion; Cytokine; ELISA; ERK1/2; FBGC; FITC; IL10; IL6; JNK; LPS; Lipopolysaccharide; MAPK; MEMκ; Multinuclear macrophage; NFATc1; NFκB; PBS; PI3K; PLCγ; Phagocytosis; RANK; RANKL; Signaling; TLR4; TNFα; TRAF6; TRAP; c-Jun N-terminal kinase; enzyme-linked immunosorbent assay; extracellular signal-regulated kinase 1/2; fluorescein isothiocyanate; foreign body giant cell; interleukin 10; interleukin 6; lipopolysaccharide; minimum essential medium alpha medium; mitogen-activated protein kinase; nuclear factor of activated T-cells, cytoplasmic 1; nuclear factor κB; phosphate-buffered saline; phosphoinositide 3-kinase; phospholipase C-γ; receptor activator of nuclear factor κB; receptor activator of nuclear factor κB ligand; tartrate-resistant acid phosphatase; toll-like receptor-4; tumor necrosis factor receptor associated factor 6; tumor necrosis factor α